With a 50% greater relative-risk of smoking attributed lung cancer than Whites, and the highest overall rates of cancer incidence and mortality in the U.S., African Americans experience disproportionately greater tobacco- related disease burden. Striking health disparities exist despite the fact that African Americans have similar smoking prevalence as Whites, yet smoke fewer cigarettes per day (cpd). In fact, over half of all African American smokers are light smokers (smoke 10 or fewer cpd). To have an impact on the premature mortality of African American smokers, effective treatment for smokers across the smoking continuum must be identified. Varenicline, the leading first-line medication for tobacco use treatment, triples the likelihood of long-term abstinence relative to placebo in those smoking >10 cpd. To date, efficacy of varenicline has not been established in African American smokers or light smokers. The long-term goal of this research is to advance treatment for all African American smokers in order to reduce tobacco-related disease and death. Our primary objective is to evaluate the efficacy of varenicline for tobacco use treatment among 500 African American smokers, including a full range of cpd, within a double-blind, placebo-controlled, randomized clinical trial. We will randomize participants in a 3:2 ratio to receive varenicline (1 mg bid; n=300) or placebo (n=200) for 12 weeks, along with individualized health education counseling for all participants. Our specific aims are to evaluate the efficacy of varenicline to promote abstinence in African American smokers across the continuum of smoking level, to examine efficacy in light smokers and also in moderate to heavy smokers, to characterize nicotine and carcinogen exposure, and to describe biopsychosocial characteristics of this group and evaluate in relation to abstinence. This innovative study will provide the first placebo-controlled evaluatin of varenicline in the full spectrum of African American smokers, and the first to examine varenicline in light smokers. Findings will contribute to advancing effective treatment for African American smokers and for light smokers, and enhancing individualized treatment. Increased treatment efficacy will have major impact on reducing tobacco- related morbidity and mortality in this high-risk population.